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About 250 million years ago,[2] during the Triassic, a new ocean began forming in the southern end of the Paleo-Tethys Ocean. A rift formed along the northern continental shelf of Southern Pangaea (Gondwana). Over the next 60 million years, that piece of shelf, known as Cimmeria, traveled north, pushing the floor of the Paleo-Tethys Ocean under the eastern end of Northern Pangaea (Laurasia). The Tethys Ocean formed between Cimmeria and Gondwana, directly over where the Paleo-Tethys used to be.

During the Jurassic Period (150 Ma), Cimmeria finally collided with Laurasia. There it stalled, the ocean floor behind it buckling under, forming the Tethyan Trench. Water levels rose and the western Tethys came to shallowly cover significant portions of Europe, forming the (first) Tethys Sea. Around the same time, Laurasia and Gondwana began drifting apart, opening an extension of the Tethys Sea between them that today is the part of the Atlantic Ocean between the Mediterranean and Caribbean. As North and South America were still attached to the rest of Laurasia and Gondwana, respectively, the Tethys Ocean in its widest extension was part of a continuous oceanic belt running around the Earth between about latitude 30° N and the Equator. Thus, ocean currents at that time—around the Early Cretaceous—ran radically differently from the way they do today.

Between the Jurassic and the Late Cretaceous (which started about 100 Ma), even Gondwana began breaking up, pushing Africa and India north, across the Tethys and opening up the Indian Ocean. As these land masses pushed in on the Tethys ocean from all sides, up until as recently as the Late Miocene (15 Ma), it continued to shrink, becoming the Tethys Seaway or (second) Tethys Sea. Also throughout the Cenozoic, global sea levels fell hundreds of meters from their previous stand, and eventually the connections between the Atlantic and the Tethys closed off in what is now the Middle East.

Paleontologists also find the Tethys Ocean particularly important because much of the world's sea shelves were found around its margins for such an extensive length of time. Marine, marsh-dwelling, and estuarian fossils from these shelves are of considerable paleontological interest. The Solnhofen limestone in Bavaria, originally a coastal lagoon mud of the Tethys Ocean, yielded the famous Archaeopteryx fossil.

Like every science, geology is a continuously evolving system of theories, and the terms used to describe various pre-historic formations have fluctuated as more accurate theories have emerged. For example, many internet sources use "Tethys Ocean" to refer to the "Tethys Sea" and vice versa. Some even appear to erroneously refer to the growing Atlantic Ocean during the Jurassic as the Tethys Sea.

During the Oligocene, large parts of central and eastern Europe were covered by a northern branch of the Tethys Ocean, called the Paratethys. The Paratethys was separated from the Tethys by the formation of the Alps, Carpathians, Dinarides, Taurus and Elburz mountains during the Alpine orogeny. It gradually disappeared during the late Miocene, becoming an isolated inland sea.

The eastern part of the Tethys Ocean is likewise sometimes referred to as Eastern Tethys.

As theories have improved, scientists have extended the "Tethys" name to refer to similar oceans that preceded it. The Paleo-Tethys Ocean, mentioned above, existed from the Silurian (440 Ma) through the Jurassic periods, between the Hunic terranes and Gondwana (later the Cimmerian terranes). Before that, the Proto-Tethys Ocean existed from the Ediacaran (600 Ma) into the Devonian (360 Ma), and was situated between Baltica and Laurentia to the north and Gondwana to the south. Neither Tethys oceans should be confused with the Rheic Ocean, which existed to the west of them in the Silurian period. To the north of Tethys sea, the then land mass was called Angaraland and to the south of it, it was called Gondwanaland.

The name is taken from the Greek mythological figure Tethys, sister and consort of Oceanus and mother of the great rivers, lakes and fountains of the world and of the Oceanid sea nymphs.

^Edward Suess (March 1893) "Are ocean depths permanent?,"Natural Science: A Monthly Review of Scientific Progress (London), 2 : 180- 187. From page 183: "This ocean we designate by the name "Tethys," after the sister and consort of Oceanus. The latest successor of the Tethyan Sea is the present Mediterranean."